title: Genetic polymorphisms in matrix metalloproteinases (MMPs) and tissue inhibitors of MPs (TIMPs), and bladder cancer susceptibility.
abstract: OBJECTIVE
  To elucidate genetic polymorphisms of the matrix metalloproteinases (MMPs) MMP1 (rs1799750), MMP2 (rs243865), MMP9 (rs3918242), MMP12 (rs2276109) and tissue inhibitors of MMPs (TIMPs) TIMP1 (rs2070584) and TIMP3 (rs9619311) genes that may be involved in susceptibility to bladder cancer (BC).
  
  
  METHODS
  We enrolled 241 patients with BC and 199 controls. Genomic DNA samples were extracted from peripheral blood and polymorphisms were analysed by high-resolution melting analysis and by real-time polymerase chain reaction using TaqMan fluorescent probes.
  
  
  RESULTS
  Of the six evaluated polymorphisms of MMPs and TIMPs, only one was found to be associated with BC risk. There was a significant difference for MMP1 (rs1799750) 2G/1G+1G/1G genotype (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.39-0.98; P = 0.042). Additionally, there was a joint effect of this genotype on BC risk among 'ever smokers' (OR 0.51, 95% CI 0.28-0.89; P = 0.019), but not in 'never smokers'. The combined genotype MMP2 -1306C/T (rs243865) allele T with MMP9 -1562C/T (rs3918242) allele T was found to increase BC risk (OR 2.00, 95% CI 1.10-3.62; P = 0.022).
  
  
  CONCLUSIONS
  Our results suggest that genetic variations in five polymorphisms of MMPs and TIMPs are not associated with a high risk of BC. Only MMP1 polymorphism may be related to the risk of BC, notably in 'ever smokers'. Our study suggests that the effects of polymorphisms of MMPs and TIMPs on BC risk deserve further investigation.
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Wieczorek
authors.forename: Edyta
authors.initials: E
authors.lastname: Reszka
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Jablonowski
authors.forename: Ewa
authors.initials: E
authors.lastname: Jablonska
authors.forename: Magdalena Beata
authors.initials: MB
authors.lastname: Krol
authors.forename: Adam
authors.initials: A
authors.lastname: Grzegorczyk
authors.forename: Jolanta
authors.initials: J
authors.lastname: Gromadzinska
authors.forename: Marek
authors.initials: M
authors.lastname: Sosnowski
authors.forename: Wojciech
authors.initials: W
authors.lastname: Wasowicz
mesh_terms: D000368:Aged; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D016017:Odds Ratio; D011044:Poland / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000235:genetics*
chemical_list: C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D020781:Matrix Metalloproteinase 1
keywords: MMP; TIMP; bladder cancer; case-control study; genetic polymorphism; susceptibility